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Testing the efficacy of antimicrobial peptides in the topical treatment of induced osteomyelitis in rats

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Abstract

Joint replacement infections and osteomyelitis are among the most serious complications in orthopaedics and traumatology. The risk factors for these infections are often bacterial resistance to antimicrobials. One of the few solutions available to control bacterial resistance involves antimicrobials, which have a different mechanism of action from traditional antibiotics. Antimicrobial peptides (AMP) appear to be highly promising candidates in the treatment of resistant infections. We have identified several AMP in the venom of various wild bees and designed analogues that show potent antimicrobial activity and low toxicity against eukaryotic cells. The aim of the present study was to test the efficacy of one of those synthetic peptide analogues for the treatment of acute osteomyelitis invoked in laboratory rats. Femoral cavities of 20 laboratory Wistar rats were infected with Staphylococcus aureus. After 1 week, eight rats received an injectable calcium phosphate carrier alone, another eight rats were treated with a calcium phosphate mixed with AMP, and four rats were left without any further treatment. After another week, all rats were euthanized and radiographs were made of both the operated and healthy limbs. The animals with the carrier alone exhibited more severe acute osteomyelitis on radiographs in comparison to the recipients of the calcium phosphate carrier loaded AMP and untreated infected individuals. Based on the results of the above mentioned experiment, it was concluded that when injected directly into the site of femoral acute osteomyelitis, the calcium phosphate carrier mixed with AMP reduced osteomyelitis signs visible on radiographs.

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Acknowledgments

This work was supported by the Czech Health Research Council (AZV ČR, grant number 16-27726A), by the Technology Agency of the Czech Republic (grant number TA04010638), by research project RVO 61388963 of the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, and by internal grant numbers 9777 (Advanced therapies) and 6010 of the Motol University Hospital. We thank Dr. Radek Šerý from the National Institute of Public Health for his help with the experiments on laboratory animals and for performing radiography. We also thank to Mr. Tim Lioyd for assistance with the English.

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Authors and Affiliations

  1. Department of Orthopaedics, First Faculty of Medicine, Charles University in Prague and Motol University Hospital, V Úvalu 84, 150 06, Prague 5, Czech Republic

    Pavel Melicherčík, David Jahoda, Ivan Landor, Rastislav Ballay & Petr Fulín

  2. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic

    Václav Čeřovský & Ondřej Nešuta

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  1. Pavel Melicherčík
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  2. Václav Čeřovský
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  3. Ondřej Nešuta
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  4. David Jahoda
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Correspondence to Pavel Melicherčík.

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All applicable international, national, and institutional guidelines for the care and use of animals were followed. The experiments with animals were carried out in the research and breeding facility of the National Institute of Public Health in Prague, under conditions that comply with Regulation No. 419/2012 of the Ministry of Health as last amended. All procedures performed in studies were in accordance with the ethical standards of this institute.

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Melicherčík, P., Čeřovský, V., Nešuta, O. et al. Testing the efficacy of antimicrobial peptides in the topical treatment of induced osteomyelitis in rats. Folia Microbiol 63, 97–104 (2018). https://doi.org/10.1007/s12223-017-0540-9

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